Despite the massive improvements in scale-up enabled by single-use bioreactors and a scale-out philosophy, going from process development scale to larger bioreactors remains tricky. That’s especially true when responsibilities are transferred among academic labs, contract development and manufacturing organizations (CDMOs), and biopharma companies, each of which may use different equipment.
Arsenale Bioyards recognized the inefficiencies and developed a platform that could radically change biomanufacturing, much like the Bessemer converter in the mid-19th century transformed the steel industry, making mass production not only possible but also cost-effective.
Traditionally, production processes are designed around a molecule. Arsenale reverses that workflow, focusing first on manufacturing. “By inverting the process, you can standardize the industrialization part…which brings down the cost massively,” Massimo Portincaso, MD, CEO, tells GEN.
“We bring the industrial conditions to the lab and let biologists design directly in a manufacturing environment,” Portincaso stresses. Therefore, developers can optimize a yeast-based expression platform around Arsenale’s production system and take it from lab to commercial-scale using the exact same processes and bioreactors.
Managing variables
To further streamline development, Arsenale leverages natural interdependencies among organisms, “rather than brute-forcing” molecule design. That approach presents many more design possibilities, says Portincaso. AI-enhanced organism and process design sorts through those alternatives, considering natural codependences and interrelationships, to find the options that are best-suited to industrialization.
High-sensitivity monitors, incorporated early during process development, provide real-time insights into critical process parameters. The resulting precision fermentation reduces development time and makes it easier to meet current good manufacturing practices. This overall approach, Portincaso says, “guarantee[s] that what you’re doing in the lab will scale industrially.”
Like a growing number of biotechs, Arsenale advocates scaling-out—rather than scaling-up—biomanufacturing. To do this, “We use AI to decompose the big industrial settings into sub-parts, run batteries of small bioreactors, and then recombine them, using AI to predict industrial-scale performance,” Portincaso says. This lets designers select not only the best molecule but also the best processing parameters. “For more capacity, we just add [additional] bioreactors.”
Using that process, “We aspire to cut costs by 90%,” he says. “We’re not there yet, but there’s a lot of room for innovation in the non-biopharma space and eventually also in biopharma.”
Biotech developers wanting to adopt this approach should do so as early as possible, Portincaso says. Ideally, that’s as soon as they achieve adequate output from their yeast-based expression platform. That’s because the lab and industrial infrastructures are tightly intertwined. To maximize the potential benefits, “It’s not [just] that you design in an industrial setting,” he explains, “but that you design in our industrial setting.”
That may sound self-serving, but Portincaso promises there’s a valid reason for his statement. Calibrating process development to this one setting provides a definite start and end point that limits the number of possible variables, he explains. Consequently, he says, “AI-based process development prediction becomes computationally tractable.”
Not a CDMO+
Arsenale’s business model appears to resemble a CDMO+ contract research organization (CRO), but Portincaso maintains that’s not the case. The key difference, aside from a “manufacturing-before-molecule” approach, is that Arsenale provides an enabling platform that biopharma manufacturers would use themselves.
“Biomanufacturers would develop the process and would own all of the data and the processes that are developed, so the learning stays with them,” Portincaso points out. The core platform isn’t ready for broad commercial use, but once it is solidified Portincaso says he plans to out-license it.
The first users are most likely to be food and cosmetics biomanufacturers, which are held to somewhat less stringent regulations than the pharmaceutical industry.
New, but fast
Arsenale began operations in January 2024. Since then, it has built its first bio-facility using two 500-liter bioreactors, has developed the first and second iterations of batteries of 50-milliliter microbioreactors with precision-sensing capabilities, and has generated data to validate its AI algorithm.
Next, it aims to increase staff size by nearly 50% and build a pilot facility in 2026 or 2027 to handle production runs of 10,000 liters and, eventually, 60,000 liters. In 2029, “at the latest,” Portincaso says, he plans to establish a production-scale facility.
Last February, Arsenale announced it had closed its first seed-financing round. The $10 million raise will help the organization expand its infrastructure and speed commercialization for, initially, the food and cosmetics markets.
Despite this progress, this fledgling company is still trying to prove itself to the industry and potential investors. Some investors question whether micro-reactors can accurately predict the behavior of production platforms at industrial scale, Portincaso admits. But, he says, “We know this is possible, because some companies are doing something very similar.” The more pressing concerns, he says, are simply generating data in a timely manner and fine-tuning the sensing capabilities of the biomanufacturing platform to take the industry to a new stage of efficiency.
Creating a “Bessemer moment”
Generating a new approach to biomanufacturing was, Portincaso says, “a necessity.”
After years focused on deep tech at the Boston Consulting Group, he recalls, “I wanted to become an investor in this space.” He quickly realized that for him, the real excitement was in tackling projects himself, rather than raising funds so others could tackle projects.
After having co-founded a DNA/mRNA design and synthesis biopharma, Portincaso “realized the huge potential of biomanufacturing.” Deeper analysis led him to conclude that the industry’s evolution away from producing blockbuster drugs and toward relatively small batches of tightly-targeted therapeutics requires right-sizing the cost structure and manufacturing.
“We’ve been trying to produce things that cost tens of euros using the cost structure of an industry that is geared towards producing things that cost thousands of euros,” he points out. “This will always be a niche industry until somebody really changes the paradigm.”
Portincaso says he hopes Arsenale’s process will cause that paradigm shift. Specifically, he says he hopes to revolutionize the mass production of biologics just like in the mid-19th century, the Bessemer process made the mass production of steel not only possible, but cost-effective.
“What biotech needs isn’t necessarily better technology, but technology [and processes] that cost ten-fold less to increase adoption and generate more data. This is part of what we’re trying to solve,” Portincaso says.
To do this, Arsenale aims to “embrace aporia,” as its website says. The company tries to cultivate the state of curiosity needed to continually innovate.
“The more things get complex, the more you need to step back,” Portincaso says, to focus on the actual problem and find the right solution. “We have a multidisciplinary team, with people in biology, AI, engineering, and industrial contexts. Exposing them to each other challenges them, and is one way we try to practice aporia.”
